Ethanol is known to affect the excitability of the nervous system; however, the cellular mechanisms underlying such actions are poorly understood. The objectives of this project are to characterize the mechanisms regulating nerve cell excitability and the effects of ethanol on those mechanisms. Electrophysiological methods were used to characterize the membrane mechanisms that underlie excitable phenomena. The membrane ion currents that are involved in the regulation of neuronal excitability were investigated in neurons from superior cervical and nodose ganglia using the whole- cell patch-clamp technique, in striatal neurons using single- channel recording and in hippocampal pyramidal neurons using the single-electrode voltage-clamp method. Two different sodium currents were characterized in the neurons from nodose ganglion: tetrodotoxin (TTX)-sensitive and TTX-resistant. The nodose neurons also have two calcium currents, transient and sustained. By contrast, the sympathetic neurons have only a TTX-sensitive sodium current and a sustained calcium current. At least three different potassium currents have been characterized in the sympathetic neurons: voltage-activated transient, delayed rectifier, and sustained calcium-activated. Similar potassium currents have been characterized in hippocampal CA3 pyramidal neurons. Studies of transmitter regulation of these currents has revealed that the sustained calcium-activated potassium current in hippocampal neurons is inhibited by muscarinic receptor activation, single potassium channels are opened by dopamine in striatal neurons, and the calcium current in sympathetic neurons is inhibited by somatostatin. The effect of ethanol on these currents is currently being investigated. The significance of the project lies in the fact that the identification of the mechanisms involved in nerve cell excitability and the investigation of the action of ethanol on those mechanisms holds the promise of increasing our understanding of the cellular basis of ethanol's actions in the nervous system.